Racemic and enantiomerically pure amines play a dominant role in numerous complex natural substances, such as e.g. the alkaloids, vitamins or amino acids, the chemical, pharmaceutical and industrial importance of which is undisputed. As chemical intermediates, amines find applications in the synthesis of pharmaceuticals, agrochemicals, food additives, colours or cosmetics, among other sectors. For the active substances sector, amino acids and amino alcohols play a dominant role.
For the synthesis of non-functionalised and functionalised amines, the reductive amination (hydroamination) of ketones and aldehydes plays a large part. Considerable preparative and technical importance is attached to catalytic reduction with hydrogen (W. S. Emerson in Organic Reactions, Vol. 4, John Wiley & Sons, New York, 1948, pp. 174–255, Rylander Catalytic Hydrogenation over Platinum Metals, Academic Press, New York, 1967, pp. 291–303; Catalytic Hydrogenation in Organic Synthesis, Academic Press, New York, 1979, 165 ff; M. V. Klyuev, M. L. Khidekel Ruiss. Chem. Rev. 1980, 49, 14–27; Rylander Hydrogenation Methods; Academic Press, New York, 1985, pp. 82–93; V. A. Tarasevich, N. G. Kozlov Ruiss. Chem. Rev. 1999, 68, 55–72). The use of hydrogen as a reducing agent requires high-pressure apparatus, which involve high operating costs and represent considerable technical complexity in the construction and operation of suitable plants.
Reductions with metal hydrides, such as sodium borohydride (G. W. Gribble Chem. Soc. Rev. 1998, 27, 395–404), sodium cyanoborohydride (R. O. Hutchins, N. R. Natale Org. Prep. Proceed. Int. 1979, 11, 201) or sodium triacetoxyborohydride (A. F. Abdel-Magid, C. A. Maryanoff in Reductions in Organic Synthesis, ACS Symp. Ser. Vol. 641, 1996, 201–216), generally take place under milder conditions, but are associated with considerable problems such as risk of explosion and toxicity.
Other reducing agents, such as aluminium or zinc (F. Möller, R. Schröter in Houben-Weyl, Methoden der Organischen Chemie, vol. XI/1, ed. E. Muller; Thieme Verlag, Stuttgart, 1957, 667–669), and electrolytic reduction (Yu. D. Smirnov, L. A. Fedorova, A. P. Tomilov Elektrokhimia 1992, 28, 588–599), are of lesser importance. The production of chiral amines in this case requires the use of stoichiometric quantities of chiral auxiliary compounds, which are often difficult to obtain, and usually their subsequent separation.
Very high optical yields are achieved in enzymatic transamination (R. O. Duthaler Tetrahedron. 1994, 50, 1539–1650). However, the method is mainly restricted to the production of amino acids. In addition, the corresponding amines can be obtained only with difficulty. Furthermore, the separation of the aqueous buffer solutions involves high costs.
In reductive amination according to Leuckart-Wallach (M. L. Moore in Organic Reactions, Vol. 5, John Wiley & Sons, New York, 1949, pp. 301–330), formic acid is used as the reducing agent. On a laboratory scale, the use of the easy to handle organic hydrogen donors as reducing agents is well proven, as these are non-explosive and of low toxicity. By varying these hydrogen donors, the selectivity of the amination reaction can also be influenced. The Leuckart-Wallach reaction is accelerated by adding support-bound, heterogeneous hydrogenation catalysts such as nickel or cobalt (A. N. Kost Nauch. Doklady Vysshei Shkoly, Khim. I Khim. Tekhnol. 1958, 125–129, C. A. 1959, 53, 3112i), nickel-aluminium alloys or Raney nickel (DRP 861844 (1943), Chem. Zentralblatt, 1953, 5926).
Lewis acids, such as magnesium chloride, zinc chloride, iron chloride (J. F. Bunnett, J. L. Marks J. Am. Chem. Soc. 1949, 71, 1587–1589) or aluminium chloride (U.S. Pat. No. 4,851,548) also catalyse the amination of carbonyl compounds. In this case, the reaction of ketones only takes place with satisfactory yields at high temperatures of 150 to 200° C. With the catalysts described, however, it is not possible to perform an enantioselective reaction.